Wednesday, November 14, 2007

I fear I am boring people over at Brad's blog so I am taking the debate here and to the post below which is long and almost irrelevant.

Sebastian writes

"As for the idea that NIH funds 'most' of the research, I strongly suggest that you look around Derek Lowe's blog at http://www.corante.com/pipeline/

He has a number of good posts on the subject. I would look on the right hand side under "Categories" and consider:"Me Too" DrugsAcademia (vs. Industry)Drug DevelopmentDrug Industry HistoryPatents and IP

(though if you want an overview, the first 2 categories are probably enough)."

His overall point is that the contributions of the NIH aren't the 'near-none' that some hyper-market advocates may say, but they aren't anywhere near as important in drug development as people like Waldmann or Angell seem to think.

I am working through the category "Acadamia (vs. Industry)". I find the blog very interesting and my angry co-author is going to be even angrier tomorrow.

I have read back to September 2004 and I finally get to some data on quantity of research. More recent posts (discussed at great length below) note that some academics don't do drug development and that academics tend to make exaggerated claims that their research will be useful for drug development.

Lowe writes

OK, I couldn't resist. Let me reiterate that I completely admire the NIH's commitment to basic research; it's one of the real drivers of science in this country. But they're not a huge factor in clinical trials. Academia does more basic research than pharma; pharma does more clinical work than academia. Here are some statistics from a reader e-mail:

Now we get to the data. He quotes an e-mail

Regarding the clinicaltrials.gov numbers, by my reckoning the 8000 NIH studies and the 2400 'industry' studies probably represent about the same investment in *therapeutic* clinical trials. If you break down the NIH trials, about 1800 (22%) are Phase I, 3000 (37%) are Phase II, 1100 (14%) are Phase III, and the rest (2150, 27%) are observational and other. (If you want to check, I did a search within the results for the appropriate phrases and subtracted from the total for the remainder). Figures for industry are 460 (19%) Phase I, 1060 (44%) Phase II, 770 (32%) Phase III, and 133 (5%) other.

In my experience each phase of clinical trials multiplies costs by about 10 times (e.g., Phase I = X; Phase II = 10X, Phase III = 100X), so the clinicaltrials.gov figures imply that the costs of Phase I, II, and III trials funded by industry are over 80% of those funded by NIH (costs are overwhelmingly driven by Phase III trials). And this is despite the close to 100% capture of NIH trials versus the unknown percentage capture of industry trials that you noted in your post."

OK so the evidence that "pharma does more clinical work than academia." is a study in which there are 8000 NIH studies and 2400 pharma studies. All the studies are clinical with human patients. Back at Brad's blog, I suggested that pharma has a massive lead in Phase III trials. The data show 1100 NIH funded phase III trials and 770 industry funded phase III trials.

The conclusion is based on the argument that "the close to 100% capture of NIH trials versus the unknown percentage capture of industry trials that you noted in your post." That is, the data suggest that the NIH does more clinical research than , but we assume the data are biased so we conclude that industry does more clinical research than academia. Note not all academic research is NIH funded.

When an actual statistic enters Lowe's blog, he concludes that it is misleading because ... well I will read his argument.

Next post shows that Lowe's identification of NIH funded with academia is not sloppy. It is grossly dishonest. He quotes Encephalon.

"Using arguably one of the best (databases) we've got (the NIH's ClinicalTrials.gov**) we get the following figures: of the 15,466 trials currently in the database, 8008 are registered as sponsored by NIH, 380 by 'other federal agency', 4656 by 'University/Organization', and 2422 by Industry."

Lowe says he is suspicious of the data base and, in particular, the "University/Organization" classification. That is he rejects the evidence, although he presents none of his own.

"I agree that NIH has a real role in clinical trials, but I don't think it's a large as these figures would make you think. Clinicaltrials.gov, since it's an NIH initiative, is sure to include everything with NIH funding, but there are many industry studies that have never shown up there. (And I share the scepticism about the "University" designation.)"

OK if they are many, name one.

My understanding is that clinical trials require pre-approval by the FDA -- an IND for "investigative new drug." I see no reason why the FDA would miss many clinical trials and no basis for Lowe's apparent beleif that the NIH didn't get information from the FDA.

Lowe is a scientist. I don't see how he can assert that there are "many" of something without a shred of evidence.

A post on oral anti diabetic drugs and ppars. Does show that some things started at a Japanese pharmaceutical company and Glaxo made an important basic science type contribution.

Next post is on "does pharma do basic research" so the example above would be an important case of "yes". It means the post I discuss just above was written to prove that pharma does some basic research.Also Lowe notes his own contribution to synthetic organic chemistry building on work by Bristol-Meyers Squibb.

A very long post on the "doo-dah kinase" a made up enzyme. In Lowe's story academics do not work on a drug which inhibits the doo-dah kinase. Roughly academics are biologists and chemists are in industry. This is a useful way for him to present his claim, but it has nothing to do with evidence.

A post on patents and should Universities apply for them (or refrain for the public good)

A post on how most people in the academy are graduate students and younger than people in industry (roughly).

A post on how Stuart Schreiber thinks that academics shouldn't try to develop drugs. Note Stuart Schreiber is criticizing an NIH initiative. The argument basically is that pharma does this.

Two more posts on what it is like to get a PhD in chemistry vs working in industry.

The first post in the archive

Greg Hlatky over at A Dog's Lifeis right on target in his post of Tuesday the 24th. And that's not just because he said that my posts always make him think - of course, he could always be thinking "What's with this maniac, anyway?"

No, he's completely correct about the uses of time and money in academia versus industry. He points out that:

Industry and academia each have major constraints. At colleges and universities, it's money. Money is always in short supply and grants have to be used to cover the administration's greed in charging overhead, tuition and stipend for the students, purchase of laboratory chemicals and equipment, and so on. The money never seems enough and professors are always rattling their begging cups with funding agencies to continue their research.

Does sound like moving some money from industry to the academy would be a good idea no ? But Holsclaw sent me here to convince me of the opposite didn't he ?

following Holsclaw's link, I discover that I have massively overestimated industries role in phase III trials, an important kind of clinical research.

Someone clearly chosen as a critic of the "NIH does the real research" view is of the opinion that money is wasted in industry and in short supply in the academy. That the transfer of projects from the academy (research) to industry (development) is inefficient because academics are totally out of touch with development and that, therefore, academics should not develop expertise in drug development (huy?).

It all sounds like an overwhelming case for bargaining down prices of pharmaceuticals to provide enough money so that academic chemists can work with academic biologists and physicians doing what pharma does at a much much much lower cost.

Now I remain convinced (as I wrote in comments upstream from Holsclaw's in Brad's blog) that the pharmaceutical industry plays a crucial role in drug development (the R in R&D will not get us to an Rx without interacting with the D). There is, however, no systematic evidence for this claim in the blog archive category industry vs academia.

I can't believe that any claim could be so weak that someone would link to a mass of opinion in which the only solid facts point strongly against that claim (the known fact, as always, is that the numbers are in the database, not that they are exact).

I haven't read the first category "copy cat drugs" and I don't plan too. I have spent much time tonight exploring the question of whether it is wise to pay any attention to Sebastian Holsclaw, and I have reached a very firm conclusion.